Antibiotic Regimens Research Articles

Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

Primary delayed sternal closure in adult cardiac surgery: a systematic review of protocols.

Primary delayed sternal closure (DSC) is a useful tool in the management of certain critically unstable patients after cardiac surgery, but there is a paucity of consensus management guidelines. This review aimed to identify critical key areas in DSC management. Systematic literature search was conducted in January 2023 and performed using Embase and PubMed. For original research articles were included that described outcomes and/or protocols for primary adult DSC patients, excluding articles on pediatric patients and secondary DSC. Eleven retrospective review original articles examined protocols for adult patients undergoing DSC. Hemodynamic instability and uncontrolled bleeding/coagulopathy were the two most common indications. Time to chest closure ranged 22 hours - 8.7 days. A range of dressings were employed, including Esmark and VAC dressings, with about half of authors not disclosing details. VAC was endorsed by several authors specifically for management of uncontrolled hemorrhage/coagulopathy. There was no consensus regarding irrigation solution for mediastinal prepping, with or without antibiotic solution. There was a lack of consensus on antibiotic selection and duration, varying from 2 and 3 multidrug regimens of broad-spectrum antibiotics, with/without antifungals. Mediastinal re-exploration varied from undefined intervals to regimented 24-48-hour interval re-explorations, with final closures in the OR or ICU. The optimum care for the patient with an open chest is evolving, and although there is a lack of a consensus DSC protocol, this review identifies mediastinal management, antimicrobial prophylaxis, and mediastinal re-exploration schedules/protocols as key areas for study to determine optimal care for DSC patients.

Antibiotic Susceptibility-Guided Concomitant Therapy Regimen with Vonoprazan, High-Dose Amoxicillin, Clarithromycin, and Metronidazole for Helicobacter pylori Eradication as Fourth-Line Regimen: An Interventional Study.

Twenty patients who underwent three rounds of eradication therapies (first- or second-line 7-day triple therapy consisting of amoxicillin and clarithromycin, or metronidazole- and sitafloxacin-based third-line therapy) and had failed eradication based on a urea breath test or fecal antigen test were recruited. All patients underwent endoscopic examination and culture tests before starting eradication therapy. The intervention was concomitant therapy consisting of vonoprazan 20 mg bid, amoxicillin 500 mg qid, clarithromycin 400 mg bid, and metronidazole 250 mg bid for 14 days, which were modified based on the susceptibility test, and the resistant drugs were removed from the regimen. Patients with negative culture results were treated with quadruple therapy. The primary outcome was the eradication rate (UMIN000025765, jRCTs 031180208). The eradication rate of susceptibility-testing-based fourth-line eradication therapy was 63.2% (95%CI: 38.4-83.7%) in intent-to-treat analysis and 70.6% (95%CI: 44.0-89.7%) in per-protocol analysis. Thirteen patients received quadruple therapy, with eradication rates of 61.5% and 75.0%, respectively. No serious adverse events were reported. This vonoprazan-based concomitant therapy modified by the susceptibility test is a potential option as fourth-line eradication after first-line clarithromycin-based 7-day triple, second-line metronidazole-based 7-day triple, and third-line sitafloxacin-based 7-day triple therapy failure.

Association of empiric antibiotic selection and clinical outcomes in hospitalised children with severe orbital infections: a retrospective cohort study

ObjectiveTo determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections.DesignMulti-centre observational cohort study using data from 2009 to 2018 clinical records.SettingCanadian...

Application of the estimand framework for an emulated trial using reference based multiple imputation to investigate informative censoring

BackgroundThe ICH E9 (R1) addendum on Estimands and Sensitivity analysis in Clinical trials proposes a framework for the design and analysis of clinical trials aimed at improving clarity around the definition of the targeted treatment effect (the estimand) of a study.MethodsWe adopt the estimand framework in the context of a study using “trial emulation” to estimate the risk of pneumocystis pneumonia, an opportunistic disease contracted by people living with HIV and AIDS having a weakened immune system, when considering two antibiotic treatment regimes for stopping antibiotic prophylaxis treatment against this disease. A “while on treatment” strategy has been implemented for post-randomisation (intercurrent) events. We then perform a sensitivity analysis using reference based multiple imputation to model a scenario in which patients lost to follow-up stop taking prophylaxis.ResultsThe primary analysis indicated a protective effect for the new regime which used viral suppression as prophylaxis stopping criteria (hazard ratio (HR) 0.78, 95% confidence interval [0.69, 0.89], p < 0.001). For the sensitivity analysis, when we apply the “jump to off prophylaxis” approach, the hazard ratio is almost the same compared to that from the primary analysis (HR 0.80 [0.69, 0.95], p = 0.009). The sensitivity analysis confirmed that the new regime exhibits a clear improvement over the existing guidelines for PcP prophylaxis when those lost to follow-up “jump to off prophylaxis”.ConclusionsOur application using reference based multiple imputation demonstrates the method’s flexibility and simplicity for sensitivity analyses in the context of the estimand framework for (emulated) trials.

Antibiotic Prophylaxis and Treatment for Cardiac Device Infections.

Cardiac device infections (CDIs) are a serious complication in patients with implanted devices, resulting in increased morbidity, prolonged hospital stay, and increased healthcare costs. The effective management of these infections involves a combination of appropriate antibiotic therapy and preventive strategies aimed at reducing the risk of infection. The role of antibiotic prophylaxis in infection prevention is crucial, including the emerging use of antibiotic-supported tools and other local antibiotic delivery systems, which may reduce the risk of infection at the device implant site. In this contemporary review, we provide an overview of the prophylactic treatment and different antibiotic regimens for the treatment of CDIs, emphasizing early diagnosis, appropriate choice of antibiotics, and individualized treatment.

FREQUENCY OF PIPERACILLIN/TAZOBACTAM RESISTANCE IN SPONTANEOUS BACTERIAL PERITONITIS PATIENTS

Spontaneous bacterial peritonitis (SBP) is a serious infection in patients with chronic liver disease, requiring prompt antibiotic therapy. Due to growing resistance to first-line antibiotics like ceftriaxone, piperacillin/tazobactam is often used as a second-line treatment. However, emerging resistance to piperacillin/tazobactam poses a significant clinical challenge. Identifying local resistance patterns is crucial for optimizing treatment, particularly in resource-limited settings like Peshawar, Pakistan. Objective: To determine the frequency of piperacillin/tazobactam resistance among patients with spontaneous bacterial peritonitis at a tertiary care hospital in Peshawar, Pakistan. Methods: This cross-sectional study was conducted over five months at Lady Reading Hospital, Peshawar from 18th April to 18th September. A total of 169 patients aged 16 to 75 years with SBP secondary to chronic liver disease were included using non-probability consecutive sampling. Demographic and clinical data were collected, and ascitic fluid samples were cultured to assess resistance to piperacillin/tazobactam. Data were analyzed using descriptive statistics and chi-square tests to examine associations. A p-value &lt; 0.05 was considered statistically significant. Results: Piperacillin/tazobactam resistance was found in 9.5% (16/169) of SBP patients. Resistance was observed in 8.0% (7/88) of Escherichia coli isolates and 11.1% (9/81) of other bacterial isolates (p = 0.04). Resistance rates were slightly higher in the 46–75 age group (11.0%, 11/100) compared to the 16–45 age group (7.3%, 5/69). Male patients had a resistance rate of 10.2% (11/108), while female patients showed 8.2% (5/61). Conclusion: This study highlights significant resistance to piperacillin/tazobactam among SBP patients in Peshawar, particularly in non-E. coli bacteria. These findings underline the need for personalized antibiotic regimens and ongoing surveillance to address growing antimicrobial resistance in chronic liver disease patients.

Comparative analysis of international and Malaysia approaches to the treatment of patients with chronic gastritis from the point of view of evidence-based medicine

Background: Chronic gastritis, often resulting from *Helicobacter pylori* infection, is a widespread gastrointestinal disorder. The condition requires evidence-based treatment approaches to ensure effective management and improved patient outcomes. This study conducts a comparative analysis of the treatment approaches for chronic gastritis in Malaysia and internationally, focusing on adherence to evidence-based medicine (EBM) practices. Understanding the similarities and differences in these approaches is critical for enhancing Malaysia's healthcare strategies. Methods and Materials: The study employed a systematic review of relevant literature sourced from global medical databases, including PubMed, Embase, and Cochrane Library. The review focused on therapeutic options, diagnostic standards, and evidence-based protocols for managing chronic gastritis, with emphasis on both international and Malaysian healthcare systems. Studies included in the review primarily focused on adult patients diagnosed with chronic gastritis and treated using evidence-based methodologies. Results: The analysis revealed significant parallels in the treatment protocols between Malaysia and international guidelines, particularly in the use of proton pump inhibitors (PPIs) and antibiotic regimens for *H. pylori* eradication. However, differences emerged in the implementation of advanced diagnostic tools, accessibility of healthcare services, and the influence of local antibiotic resistance patterns. While Malaysia follows global best practices, rural-urban healthcare disparities impact the consistency of treatment delivery and patient outcomes. Conclusion: Both international and Malaysian approaches to chronic gastritis prioritize evidence-based medicine. The findings suggest that Malaysia effectively adapts international guidelines to its local healthcare context, though improvements are needed in addressing healthcare accessibility and antibiotic resistance. Enhanced implementation of EBM practices, particularly in rural areas, and personalization of treatment based on resistance patterns, could further optimize patient outcomes in Malaysia.

Antibiotics for surgical site infections in patients undergoing orthognathic surgery.

PubMed, Embase, Web of Science and Scopus. Randomized Controlled Trials (RCTs) for patients undergoing orthognathic surgery of any type, which evaluated surgical site infections (SSI) in either: long-term (at least 2 days) post-surgical antibiotic dosing versus short term (one day) post-surgical dosing for the same drug; or Orthognathic surgery patients administered a post-surgical single-day antibiotic versus a singular pre-operative dosing of any antibiotic in the post-surgical phase. Singe-arm studies, retrospective studies, unpublished data, studies which were not peer-reviewed, editorials and trials not dealing with patients undergoing orthognathic surgery specifically were not included. Data for the publication year, primary author name, location of the study, antibiotic type, antibiotic protocol with its type, dosing and timing, sample size, protocol of the control group, male gender, age, diagnosis and rates of SSIs were extracted from the included studies. Pooled rates of SSIs were utilized to produce risk ratio (RR). A total of eleven RCTs met the inclusion criteria. As per the meta-analysis, post-orthognathic surgery SSI risk was reduced significantly as a result of long-term prophylactic antibiotic usage when compared to short-term utilization. Further, the meta-analysis demonstrated that there was a significant reduction of SSI risk in patients on a single day prophylactic antibiotic regimen in comparison to those on a single preoperative antibiotic dose. The study observed that long-term (2-7 days) prophylactic antibiotics reduce SSI risk when compared to antibiotic administration over a single day. In turn, it was also found that the latter was of greater benefit over a pre-operative single antibiotic dosage.

Antibiotic Appropriateness for Urinary Tract Infections in Children.

We examined local prescribing patterns across the entire treatment course for children treated for uncomplicated urinary tract infection (UTI) to determine opportunities for antibiotic stewardship initiatives. We conducted a retrospective review of emergency department and inpatient encounters for febrile and afebrile UTI in a children's hospital from 2021 to 2022. An antibiotic spectrum ranking was established, and providers' choices were assessed for appropriateness on the basis of the individuals' urine culture (UCx). Groups were stratified by fever presence and compared using χ2, Fisher's exact, and Mann-Whitney U tests. Of 172 encounters (83% emergency department), 99 (58%) had a positive UCx. Eighty (80%) grew Escherichia coli, with 67 (84%) being susceptible to cefazolin (minimum inhibitory concentration ≤16 mg/L). There were 229 antibiotic regimens and 39 (17%) were appropriate. Inappropriate antibiotic choices included unnecessary use of broad-spectrum antibiotics and misdiagnosed UTI. Grouping by encounter, at least 1 dose of a third cephalosporin was given in 51% of encounters, and 80% of these received it unnecessarily because of UTI misdiagnosis or suitability of a narrower-spectrum antibiotic. The median prescribed antibiotic duration was 7 days (interquartile range 7-10). Of 73 encounters with UCx growing mixed flora or a nonuropathogen, only 29 (40%) had antibiotics discontinued. Confirmed UTI was associated with fever and nitrite positivity. Our study revealed high prevalence of inappropriate antibiotics, particularly unnecessary prescribing of third cephalosporin, prescriptions not supported by laboratory data, and prolonged treatment courses. Our results identify factors that can be used to support UTI treatment pathways and ensure antibiotic stewardship.

Systematic review on oral antibacterial relay therapy for acute staphylococcal prosthetic joint infections treated with debridement, antibiotics and implant retention (DAIR).

The management of acute prosthetic joint infections (PJIs) often involves a debridement, antibiotics and implant retention (DAIR) strategy. Our objective was to conduct a systematic review and a network meta-analysis (NMA) to assess the comparative effectiveness of available oral antimicrobial regimens for the treatment of acute staphylococcal PJIs treated with DAIR. We conducted a systematic review searching articles from databases creation until 31 December 2023. We included articles on acute staphylococcal PJIs managed with DAIR with an oral antibiotic regimen relaying the initial management. The primary outcome was the remission rate. Out of the 2421 studies screened, six studies completed the systematic review criteria: one randomized controlled trial and five observational studies. There was heterogeneity in patients' populations, duration and posology of treatments, definition of outcome and length of follow-up. Studies revealed 10 antibiotic regimens and most data focusing on five combinations recommended by the IDSA's guidelines: rifampicin associated to fluoroquinolone, clindamycin, cycline, linezolid or trimethoprim-sulfamethoxazole. Treatment comparisons were often secondary, without adjustment for confounding factors, resulting in a high risk of bias. Owing to inconsistencies a complete analysis, including an NMA was not possible. The available data highlight five companions to rifampicin, however, there is insufficient evidence to compare them. The literature does not provide a basis for rationalizing alternatives when rifampicin cannot be used.

Central line-associated bloodstream infection outbreak related to Ralstonia pickettii-contaminated saline in a pediatric hematopoietic stem cell transplant center.

Ralstonia pickettii is an aerobic Gram-negative non-fermentative bacillus. It is an opportunistic pathogen that has recently prompted nosocomial outbreaks. Although it has low virulence, it can cause a wide range of invasive diseases in immunosuppressive patients. The characteristics of R. pickettii-related central line-associated bloodstream infection (CLABSI) outbreak in pediatric hematopoietic stem cell transplant (HSCT) recipients are presented in this study. This was a single-center, retrospective analysis conducted at Bahcesehir University Goztepe Medicalpark Hospital . The clinical and laboratory characteristics of twelve children with Ralstonia-related CLABSIs were analyzed. Of the twelve patients with R. pickettii growth, seven were female. The median age was 12.1 (2-17) years. Autologous HSCT was performed in two of the patients and allogeneic HSCT was performed in ten patients for both malignant and non-malignant diseases. In the conditioning regimens, all patients were given myeloablative therapy. Clinical sepsis was the most common presentation. As a result of the investigations, R. pickettii growth was observed in saline solutions. All cases were successfully treated with the appropriate antibiotic regimen and the bacteria was not found in repeat cultures. Catheter removal was required in two patients. Mortality was not observed in any patient as the outcome of the infection episode. The detection and control of the infectious source are critical in pediatric HSCT patients with severe immunosuppression, as medical equipment-related outbreaks can be life-threatening.

The clinical application of metagenomic next-generation sequencing in immunocompromised patients with severe respiratory infections in the ICU.

Early targeted antibiotic therapy is crucial for improving the prognosis of immunocompromised patients with severe respiratory infections (SRIs) in the intensive care unit (ICU). Metagenomic next-generation sequencing (mNGS) has shown significant value in pathogen detection, but research on lower respiratory tract microorganisms remains limited. This study enrolled 234 patients with SRIs in the ICU, and individuals were categorized into immunocompromised and immunocompetent groups. We compared the diagnostic performance of mNGS using bronchoalveolar lavage fluid (BALF) with conventional microbiological tests (CMTs) and analyzed the value of mNGS in immunocompromised patients with SRIs in the ICU. Among all patients, the pathogenic microorganism detection rate of mNGS was higher than that of CMTs (94.02% vs 66.67%, P < 0.05), both in the immunocompromised group (95.0% vs 58.75%, P < 0.05) and the immunocompetent group (93.51% vs 71.43%, P < 0.05). mNGS detected more pathogens than CMTs did (167 vs 51), identifying 116 organisms that were missed by CMTs. The proportion of antibiotic regimen adjustments based on mNGS results was significantly higher compared to CMTs in both the immunocompromised (70.00% vs 17.50%, P < 0.05) and immunocompetent groups (48.70% vs 15.58%, P < 0.05). In the immunocompromised group, patients who had their antibiotic treatment adjusted on mNGS results had improved prognosis, with significantly lower ICU mortality (8.93% vs 50%, P < 0.05) and 28-day mortality rates (30.36% vs 68.75%, P < 0.05) than CMTs. In the immunocompetent group, no statistically significant differences were observed in ICU mortality or 28-day mortality (20.00% vs 33.33%, P > 0.05; 42.67% vs 45.83%, P > 0.05). mNGS shows significant value in detecting pathogens in immunocompromised patients with SRIs in ICU. For immunocompromised patients who respond poorly to empirical treatment, mNGS can provide an etiological basis, helping adjust antibiotic regimens more precisely and thereby improving patient prognosis.

Diverticulitis evaluation and management among United States emergency departments over an eight-year period

IntroductionDiverticulitis is a common reason for presentation to the Emergency Department (ED). However, as imaging options, risk stratification tools, and antibiotic options have expanded, there is a need for current data on the changes in incidence, computed tomography (CT) performance, antibiotic usage, and disposition over time. MethodsThis was a cross-sectional study of ED patients with a diagnosis of diverticulitis from 1/1/2016 to 12/31/2023. Using the Epic Cosmos database, all ED visits for acute diverticulitis were identified using ICD-10 codes. Outcomes included total ED presentations for diverticulitis, admission rates, CTs performed, outpatient antibiotic prescriptions, and antibiotics administered in the ED for admitted patients. ResultsThere were 186,138,130 total ED encounters, with diverticulitis representing 927,326 (0.50 %). The rate of diverticulitis diagnosis increased from 0.40 % to 0.56 % over time. The admission rate declined over time from 33.6 % to 27.7 %, while the CT rate rose from 83.0 % to 92.6 %. Among those discharged, 90.4 % received an antibiotic, which remained consistent over time. Metronidazole (55.1 %) and ciprofloxacin (40.8 %) were the most commonly prescribed antibiotics, followed by amoxicillin-clavulanate (36.1 %). Among those admitted, most received either metronidazole (62.0 %), a fluoroquinolone (40.4 %), a third-generation cephalosporin (18.9 %), or a penicillin-based agent (38.1 %). Among both discharged and admitted patients, there was a marked shift to penicillin-based agents as the primary antibiotic regimen. ConclusionDiverticulitis remains a common ED presentation, with a gradually rising incidence over time. Admission rates have decreased, while CT imaging has become more common. Most patients receive antibiotics, though the specific antibiotic has shifted in favor of penicillin-based agents. These findings can provide key benchmarking data and inform future initiatives to guide imaging and antibiotic use.

8653 A Rare Cause of a Pituitary Mass

Abstract Disclosure: L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. I.C. Arroyo Gomez: None. J. Segarra-Villafane: None. Z. Maisonet -Feliciano: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. M. Alvarado: None. J. Feneque González, MD: None. M. Marcos Martínez, MD: None. M. Correa Rivas: None. Pituitary gland masses are the second most common tumor of the central nervous system (CNS) across all age group, as per Central Brain Tumor Registry in the United States. Most common lesions are adenomas, which can be categorized as functional and non-functional based on the presence of hormonal hypersecretion. In the differential diagnosis, there is also craniopharyngiomas, Rathke’s cleft cysts, pituitary hyperplasia, inflammatory lesions, malignancy and abscess. Pituitary abscess is a rare condition, and only 0.2-0.6% of pituitary lesions are diagnosed as abscesses.This is the case of a 42-year-old female with history of hypothyroidism, chronic sinusitis with nasal polyps, severe asthma, and chronic steroid use complicated by iatrogenic adrenal insufficiency and osteonecrosis of the hips bilaterally, who was evaluated for intractable headaches. On brain imaging was found with a pituitary macroadenoma. She denied any symptoms suggesting hypersecretion of hormones and was scheduled for transsphenoidal surgery. All hormonal work up was found within normal limits, except for prior iatrogenic adrenal insufficiency due to multiple systemic steroids courses to treat asthma exacerbation throughout her life.During surgery, upon mass resection, purulent secretions were found. Frozen section was done intraoperatively, showing respiratory epithelium, pus and actinomyces species. All infectious material was removed. Infectious Diseases services was consulted and patient was promptly started on IV antibiotics. Blood cultures were negative, and patient remained afebrile. Final pathology confirmed the presence of respiratory epithelium, actinomyces colonization and a fibrous capsule with acute and chronic inflammation. Special stains report was negative for fungi. She was discharge to continue home infusion of antibiotic regimen to complete 8 weeks of treatment.There is no specific imaging finding to identify pituitary abscesses so, most of them, are diagnosed intraoperatively. They can arise from hematogenous spread or from adjacent tissues or structures (ie. patient with meningitis or sinusitis). The condition is considered a life-threatening however, the majority of cases have a chronic course. Based on different reports, theses abscesses have a higher female predominance; the age range is between 12 to 76 years and the average period between onset of symptoms and diagnosis is 8 months on average. Most pituitary abscesses are sterile, however most common organisms isolated are: Gram-positive cocci (Staphylococcus and Streptococcus), and Gram-negative organisms such as Neisseria, Escherichia coli and Corynebacterium. The rarity of cases often leads to delayed diagnosis and treatment initiation, contributing to increased morbidity and mortality. Presentation: 6/2/2024

Postoperative outcomes after receipt of ertapenem antimicrobial prophylaxis for colon surgery: a multicenter retrospective cohort study.

To evaluate postoperative outcomes among patients undergoing colon surgery who receive perioperative prophylaxis with ertapenem compared to other antibiotic regimens. Multicenter retrospective cohort study among adults undergoing colon surgery in seven hospitals across three health systems from 1/1/2010 to 9/1/2015. Generalized linear mixed logistic regression models were applied to assess differential odds of select outcomes among patients who received perioperative prophylaxis with ertapenem compared to other regimens. Postoperative outcomes of interest included surgical site infection (SSI), Clostridioides difficile infection (CDI) and clinical culture positivity for carbapenem-resistant Enterobacteraciae (CRE). Inverse probability weights were applied to account for differing covariate distributions across ertapenem and non-ertapenem groups. A total of 2,109 patients were included for analysis. The odds of postoperative SSI was 1.56 times higher among individuals who received ertapenem than among those receiving other perioperative antimicrobial prophylaxis regimens in our cohort (46 [3.5%] vs 20 [2.5%]; IPW-weighted OR 1.56, [95% CI, 1.08-2.26], P = .02). No statistically significant differences in odds of postoperative CDI (24 [1.8%] vs 16 [2.0%]; IPW-weighted OR 1.07 [95% CI, .68-1.68], P = .78) were observed between patients who received ertapenem prophylaxis compared to other regimens. Clinical CRE culture positivity was rare in both groups (.2%-.5%) and did not differ statistically. Ertapenem use for perioperative prophylaxis was associated with increased odds of SSI among patients undergoing colon surgery in our study population, though no differences in CDI or clinical CRE culture positivity were identified. Further study and replication of these findings are needed.

Impact of Antibiotic Choice at the Time of Sacral Neuromodulation Implantation on Rates of Surgical Site Infection.

To evaluate the efficacy of specific antibiotic regimens in preventing infection following sacral neuromodulation. This is a retrospective cohort study utilizing the Premier Healthcare Database. Patients who underwent sacral neuromodulation placement between January 2016 and March 2020. The patients were grouped by those who received dual antibiotic therapy per 2019 AUA guidelines (Gram positive + broad Gram negative coverage), first- or second-generation cephalosporins or any other regimen. Comparison between groups was performed using Kruskal-Wallis and χ2 tests for continuous and categorical variables, respectively. Inverse probability of treatment weighted (IPTW) analysis was used to estimate the average treatment effect of AUA guidelines regimens versus the use the first- or second-generation cephalosporins alone. The sample included 14 179 patients, with 2211 patients receiving prophylaxis that followed the AUA guideline recommendations. There was no significant difference in surgical site infection rates within 3 months (p = 0.28) or within 12 months (p = 0.53) between the groups. On IPTW, the probability of an infection at 3 months was lower with the AUA guideline regimens compared to those who received first- or second-generation cephalosporins alone, but this difference was not statistically significant (OR = 0.73, 95% CI: [0.43, 1.24]). In the absence of allergies to cephalosporins or penicillin, first- or second-generation cephalosporins alone may be a sufficient preoperative antibiotic regimen for prevention of infection at the time of sacral neuromodulation. Not applicable due to being a database study.

Discovery of benzo[c]phenanthridine derivatives with potent activity against multidrug-resistant Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related death worldwide. Current antibiotic regimens for the treatment of TB remain dated and suffer from long treatment times as well as the development of drug resistance. As such, the search for novel chemical modalities that have selective or potent anti-Mtb properties remains an urgent priority, particularly against multidrug-resistant (MDR) Mtb strains. Herein, we design and synthesize 35 novel benzo[c]phenanthridine derivatives (BPDs). The two most potent compounds, BPD-6 and BPD-9, accumulated within the bacterial cell and exhibited strong inhibitory activity (MIC90 ~2 to 10 µM) against multiple Mycobacterium strains while remaining inactive against a range of other Gram-negative and Gram-positive bacteria. BPD-6 and BPD-9 were also effective in reducing Mtb survival within infected macrophages, and BPD-9 reduced the burden of Mycobacterium bovis BCG in the lungs of infected mice. The two BPD compounds displayed comparable efficacy to rifampicin (RIF) against non-replicating Mtb (NR-Mtb). Importantly, BPD-6 and BPD-9 inhibited the growth of multiple MDR Mtb clinical isolates. Generation of BPD-9-resistant mutants identified the involvement of the Mmr efflux pump as an indirect resistance mechanism. The unique specificity of BPDs to Mycobacterium spp. and their efficacy against MDR Mtb isolates suggest a potential novel mechanism of action. The discovery of BPDs provides novel chemical scaffolds for anti-TB drug discovery.IMPORTANCEThe emergence of drug-resistant tuberculosis (TB) is a serious global health threat. There remains an urgent need to discover new antibiotics with unique mechanisms of action that are effective against drug-resistant Mycobacterium tuberculosis (Mtb). This study shows that novel semi-synthetic compounds can be derived from natural compounds to produce potent activity against Mtb. Importantly, the identified compounds have narrow spectrum activity against Mycobacterium species, including clinical multidrug-resistant (MDR) strains, are effective in infected macrophages and against non-replicating Mtb (NR-Mtb), and show anti-mycobacterial activity in mice. These new compounds provide promising chemical scaffolds to develop potent anti-Mtb drugs of the future.

The epidemiology and microbiology of central venous catheter related bloodstream infections among hemodialysis patients in the Philippines: a retrospective cohort study

BackgroundDespite efforts to improve the management of catheter-related bloodstream infections (CRBSI) in literature, temporary CVCs continue to be used for maintenance hemodialysis outside of acute care settings, particularly in the Philippines.MethodsWe conducted a retrospective cohort study to investigate the incidence, outcomes, risk factors, and microbiological patterns of CRBSI among adult kidney disease patients undergoing hemodialysis at the Philippine General Hospital, the country's largest tertiary referral center. We included all adult patients who received a CVC for hemodialysis from January 1, 2018, to August 31, 2019, and followed them for six months to observe the occurrence of CRBSI and its outcomes.ResultsOur study documented a CRBSI incidence rate of 6.72 episodes per 1000 catheter days, with a relapse rate of 5.08%, a reinfection rate of 15.74%, and a mortality rate of 6.09%. On multivariable regression analysis, we identified autoimmune disease, dialysis frequency of > 3 × per week, use of CVC for either blood transfusion or IV medications, renal hypoperfusion, drug-induced nephropathy, and hypertensive kidney disease as significant risk factors for CRBSI. Gram-negative bacteria, including B. cepacia complex, Enterobacter, and Acinetobacter spp, were the most common organisms causing CRBSI. Multidrug-resistant organisms (MDROs) comprised almost half of the isolates (n = 89, 44.5%), with Coagulase-negative Staphylococcus species having the highest proportion among gram-positive organisms and Acinetobacter spp. among gram-negative isolates.ConclusionOur findings emphasize the need for more stringent measures and interventions to prevent the propagation of identified pathogens, such as a review of sterile technique and adequate hygiene practices, continued surveillance, and expedited placement and utilization of long-term access for patients on maintenance hemodialysis. Furthermore, CVC use outside of hemodialysis should be discouraged, and common antibiotic regimens such as piperacillin-tazobactam and fluoroquinolones should be reviewed for their low sensitivity patterns among gram-negative isolates. Addressing these issues can improve hemodialysis patients' outcomes and reduce the CRBSI burden in our institution.

A-001 The Postprandial Levels of the Metabolites in the Metaorganismal Trimethylamine N-Oxide (TMAO) Pathway are Altered in A Diet-, Microbe-, and Sex-Specific Manner

Abstract Background Cardiovascular disease (CVD) remains the leading cause of death in developed countries. Elevated levels of the gut-microbe-associated metabolite trimethylamine-N-oxide (TMAO) have been associated with increased risk for CVD mortality in many large independent studies. In fact, large laboratory corporations such as Labcorp and Quest Diagnostic now offer TMAO diagnostic tests for the assessment of CVD risk and as a marker for disease-associated dysbiosis, using samples obtained from fasting patients. Although the strong association between TMAO levels and CVD risk has been established in fasting blood samples, here we are investigating the potential for a single meal to dynamically alter TMAO-related metabolites based on sex, diverse dietary substrates, and microbial influences. Methods 35 healthy participants were randomized to one of four study groups with approximately 8-9 subjects in each arm. Half of the participants were randomly assigned to receive a three-day broad spectrum antibiotic regimen (ciprofloxacin, metronidazole, and vancomycin) while the others received no antibiotics. These two groups were further subdivided into a group consuming a highly processed meal (originating from local fast food restaurants) or alternatively a whole food meal (containing a variety of fruits, vegetables, and healthy fiber). Blood samples were taken at baseline (after an overnight fast), and then postprandially at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours after meal ingestion. Targeted plasma metabolites were quantified using a stable isotope dilution, liquid chromatography - tandem mass spectrometry (LC-MS/MS) method Results While plasma TMAO levels between food groups did not change significantly within the total cohort, there were clear individualized responses to either highly processed or whole food meals. Separation based on sex showed that TMAO levels were significantly reduced in females at 6 hours but remained steady in males for both food groups. Particularly, in the processed food group, TMAO levels were significantly lower in females than males at the 6-hour time point. Neither of these observations held true for TMAO precursors choline, carnitine, or betaine. However, plasma levels of a dietary precursor for TMAO, γ-butyrobetaine, showed clear diet-microbe-host interactions. For males in the processed food group, plasma γ-butyrobetaine levels were significantly increased in subjects on broad spectrum antibiotics. Conclusions Our results show the postprandial levels of TMAO, and its nutrient precursors dynamically change in a diet-, microbe-, and sex-dependent manner. These findings provide new insights into the postprandial levels of TMAO-related metabolites and may inform precision nutritional approaches in those who could benefit from TMAO-lowering strategies.